Role of ZBTB38 genotype and expression in growth and response to recombinant human growth hormone treatment

Samuel Parsons, Adam Stevens, Andy Whatmore, Peter Clayton, Philip Murray

Research output: Contribution to journalArticlepeer-review


Background: SNPs in ZBTB38 have been associated with idiopathic short stature (ISS) and adult height. This study sought to a) characterise the phenotype of ISS patients and their response to recombinant human growth hormone (rhGH) by ZBTB38 SNP genotype b) describe the relationship of ZBTB38 expression with normal growth and c) describe the in vitro effects of ZBTB38 knockdown on cell proliferation and MCM10 expression.
Methods: The genotype-phenotype relationship of rs6764769 and rs72401 were explored in 261 ISS patients and effects of genotype on response to rhGH were assessed in 93 patients treated with rhGH. The relationship between age and ZBTB38 expression was assessed in 87 normal children and young adults. Knockdown of ZBTB38 in SiHA cells was achieved with siRNAs and cell proliferation assessed with a WST-8 assay.
Results: rs6764769 and rs72401 are in linkage disequilibrium. rs724016 GG genotype was associated with lower birth length (p=0.01) and a lower change in height SDS over the first year of treatment (p=0.02). ZBTB38 expression was positively correlated with age (p<0.001). siRNA mediated knockdown of ZBTB38 resulted in increased cell proliferation at 72 and 96 hours post-transfection but did not alter expression of MCM10.
Conclusions: SNPs within ZBTB38 associated with ISS are linked to higher birth size within a cohort of ISS patients and a better response to rhGH therapy while ZBTB38 expression is positively related to age.
Original languageEnglish
Article numberbvac006
JournalJournal of the Endocrine Society
Issue number3
Early online date18 Jan 2022
Publication statusPublished - 1 Mar 2022


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